KGF-2 Targets Alveolar Epithelia and Capillary Endothelia to Reduce High Altitude Pulmonary Edema in Rats.
Summary of "KGF-2 Targets Alveolar Epithelia and Capillary Endothelia to Reduce High Altitude Pulmonary Edema in Rats."
High altitude pulmonary edema (HAPE) severely affects non-acclimatized individuals and is characterized by alveolar flooding with protein rich edema as a consequence of blood-gas barrier disruption. Limited choice for prophylactic treatment warrants effective therapy against HAPE. Keratinocyte growth factor-2 (KGF-2) has shown efficiency in preventing alveolar epithelial cell DNA damages in vitro. In the current study, the effects of KGF-2 intratracheal instillation on mortality, lung liquid balance and lung histology were evaluated in our previously developed rat model of HAPE. We found that pretreatment with KGF-2(5mg/kg) significantly decreased mortality, improved oxygenation and reduced lung wet-to-dry weight ratio by preventing alveolar-capillary barrier disruption evidenced by histological examination and increasing alveolar fluid clearance up to 150%. In addition, KGF-2 significantly inhibited decrease of transendothelial permeability after exposure to hypoxia, accompanied by a 10-fold increase of Akt activity and inhibited apoptosis in human pulmonary microvascular endothelial cells, demonstrating attenuated endothelial apoptosis might contribute to reduction of endothelial permeability. These results showed the efficacy of KGF-2 on inhibition of endothelial cell apoptosis, preservation of alveolar-capillary barrier integrity, and promotion of pulmonary edema absorption in HAPE. Thus, KGF-2 may represent a potential drug candidate for the prevention of HAPE. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Affiliation
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Journal Details
This article was published in the following journal.
Name: Journal of cellular and molecular medicine
ISSN: 1582-4934
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22568566
- DOI: http://dx.doi.org/10.1111/j.1582-4934.2012.01588.x
Medical and Biotech [MESH] Definitions
Blood-air Barrier
The barrier between capillary blood and alveolar air comprising the alveolar EPITHELIUM and capillary ENDOTHELIUM with their adherent BASEMENT MEMBRANE and EPITHELIAL CELL cytoplasm. PULMONARY GAS EXCHANGE occurs across this membrane.
Pulmonary Alveoli
Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place.
Ventilation-perfusion Ratio
The ratio of alveolar ventilation to simultaneous alveolar capillary blood flow in any part of the lung. (Stedman, 25th ed)
Altitude Sickness
A morbid condition of ANOXIA caused by the reduced available oxygen at high altitudes.
Fluorometry
An analytical method for detecting and measuring FLUORESCENCE in compounds or targets such as cells, proteins, or nucleotides, or targets previously labeled with FLUORESCENCE AGENTS.
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